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  3. Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice

Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice

  • Nat Commun. 2023 Apr 17;14(1):2182. doi: 10.1038/s41467-023-37968-x.
Ya-Wei Ji # 1,  Zi-Lin Shen # 1,  Xue Zhang 1,  Kairan Zhang 1,  Tao Jia 1,  Xiangying Xu 1,  Huizhen Geng 1,  Yu Han 1,  Cui Yin 1 2 3,  Jian-Jun Yang 4,  Jun-Li Cao 5 6 7,  Chunyi Zhou 8 9 10,  Cheng Xiao 11 12 13
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, China.
  • 2 Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China.
  • 3 NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China.
  • 4 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • 5 Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, China. caojl0310@aliyun.com.
  • 6 Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. caojl0310@aliyun.com.
  • 7 NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. caojl0310@aliyun.com.
  • 8 Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, China. chunyi.zhou@xzhmu.edu.cn.
  • 9 Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. chunyi.zhou@xzhmu.edu.cn.
  • 10 NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. chunyi.zhou@xzhmu.edu.cn.
  • 11 Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, China. xchengxj@xzhmu.edu.cn.
  • 12 Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. xchengxj@xzhmu.edu.cn.
  • 13 NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. xchengxj@xzhmu.edu.cn.
  • # Contributed equally.
PMID: 37069246 DOI: 10.1038/s41467-023-37968-x
Abstract

Nucleus- and cell-specific interrogation of individual basal forebrain (BF) cholinergic circuits is crucial for refining targets to treat comorbid chronic pain-like and depression-like behaviour. As the ventral pallidum (VP) in the BF regulates pain perception and emotions, we aim to address the role of VP-derived cholinergic circuits in hyperalgesia and depression-like behaviour in chronic pain mouse model. In male mice, VP cholinergic neurons innervate local non-cholinergic neurons and modulate downstream basolateral amygdala (BLA) neurons through nicotinic acetylcholine receptors. These cholinergic circuits are mobilized by pain-like stimuli and become hyperactive during persistent pain. Acute stimulation of VP cholinergic neurons and the VP-BLA cholinergic projection reduces pain threshold in naïve mice whereas inhibition of the circuits elevated pain threshold in pain-like states. Multi-day repetitive modulation of the VP-BLA cholinergic pathway regulates depression-like behaviour in persistent pain. Therefore, VP-derived cholinergic circuits are implicated in comorbid hyperalgesia and depression-like behaviour in chronic pain mouse model.

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